A newly discovered B cell subset, age-associated B cells, expresses the transcription factor T-bet, has a unique surface phenotype, and accumulates progressively with age. Moreover, B cells with these general features are associated with viral infections and autoimmunity in both mice and humans. In this article, we review current understanding of the characteristics, origins, and functions of these cells. We also suggest that the protective versus pathogenic actions of these cells reflect appropriate versus aberrant engagement of regulatory mechanisms that control the Ab responses to nucleic acid-containing Ags. Copyright © 2015 by The American Association of Immunologists, Inc.